Study of Fibro Q Index as a Non invasive Method to Predict Liver Fibrosis in Chronic Hepatitis C

Patients and methods: This study included 90 naïve patients with chronic hepatitis C who had undergone percutaneous liver biopsy before treatment and 20 healthy volunteers as a control group. FibroQ, aspartate aminotransferase (AST)/alanine amino-transferase ratio (AAR), AST to platelet ratio index, cirrhosis discriminates score, age-platelet index (API), Pohl score, FIB-4 index, and Lok’s model were calculated and compared.


INTRODUCTION
Chronic hepatitis C virus (HCV) infection is a major health problem affecting more than 170 million people worldwide.It is associated with a high risk of development of cirrhosis and hepatocellular carcinoma [1].HCV infection and its complications represent a major health problem in Egypt, where 10%-15% (about 9 million) of the general population is infected [2].Hepatitis C infection is characterized by high rates of chronicity as about 70-85% of acute HCV cases progress to chronic hepatitis [3].About 20% of chronically infected patients develop liver fibrosis and cirrhosis with subsequent progression to end stage liver disease or hepatocellular carcinoma [4].Monitoring of liver fibrosis progression is important in patients with chronic hepatitis C because it allows screening for HCC and also these patients have the most urgent need for antiviral therapy [5].Liver biopsy is recommended before starting antiviral treatment, but it has many problems as it is expensive, requires an experienced clinician, and may cause complications, including mortality in 0.018% of patients (6).In addition, sampling errors and observer variations may lead to under-staging of cirrhosis, particularly macronodular cirrhosis [7].Several noninvasive tests have been proposed to assess the severity of hepatic fibrosis as an alternative to liver biopsy.As reported by Akkayaet al. [8], there is correlation between alanine aminotransferase (ALT) levels in patients with hepatitis C virus (HCV) infection and periportal bridging/ necrosis, and Lu et al. [9] have reported that patients with cirrhosis have thrombocytopenia.Also, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) [10] and AST/ ALT ratio (AAR) [11]

PAIENTS AND METHODS
A total number of 90 naïve patients with chronic HCV were selected from 120 patients referred to Tanta Fever Hospital (Interferon Unit) in the period between July 2013 and February 2014.They were 54 males (60%) and 36 females (40%) and their ages were ranging from 24-58 years with a mean value of 40.9 years + 7.5 years as well as 20 volunteers as a control group.An informed consent was obtained before patients enter the study.Diagnosis of chronic hepatitis C was confirmed by the presence of anti-HCV antibody by enzyme immunoassay methods more than 6 months and the presence of HCV-RNA by polymerase chain reaction Subjects were categorized into 2 main groups, Group I (90 patients with CHC) and Group II (healthy control volunteers ; 20 patients).Thirty Patients with the following conditions were excluded from the study: those co-infected with human immunodeficiency virus or HBV, and those with alcohol consumption in excess of 20

Statistical analysis
Statistical analysis was performed using SPSS software version 20.Patient characteristics were represented as the mean ± SD.Bivariate Spearman's rank correlation coefficient (rs) was calculated to measure the relationship between the clinical variables and degree of fibrosis.To evaluate the diagnostic accuracies of the simple fibrosis prediction tests, their sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were done.In tests of significance, two-sided P<0.05 was considered significant.

RESULTS
There were no statistical significant differences between studied groups as regard age and sex as shown in table (1).There were significant differences between the studied groups as regard AST, ALT, Alkaline phosphatase and prothrombin time and no significant differences between the studied groups as regard serum albumin, prothrombin activity, INR, total bilirubin and direct bilirubin as shown in table (2).There were significant differences between the studied groups as regard HB%, RBCS, mean platelet volume (mpv) and platelet count and no significant differences between the studied groups as regard WBCS as shown in table (3).No significant differences were present between the studied groups as regard urea and creatinine as shown in table (4).There were significant differences between the studied groups as regard ANA titer and no significant differences between the studied groups as regard Schistosomal AB, TSH, Alpha feto-protein and random blood sugars shown in table (5).There were significant differences between the studied groups as regard APRI, CDS, FIB-4 index Fibro Q index and Pohl score and no significant differences between the studied groups as regard AAR and API as shown in table (6).There were positive correlation between Fibro Q and sex, age, AST, INR, AAR, APRI, API, CDS, FIB4 index, alkaline phosphatase, prothrombin activity, ANA titer by ELIZA, Schistosomal AB by ELIZA, HCV-RNA level (PCR),HB%, Random blood sugar, creatinine, total bilirubin and direct bilirubin and negative correlation between Fibro Q and ALT, platelets, Pohl score, serum albumin, prothrombin time and activity, Alpha feto-protein, TSH, RBCS,WBCS, mean platelet volume and urea as shown in table (7).There were 10 cases with F1 (11.1%), 54 cases with F2 (60%), 22 cases with F3 (24.4%) and 4 cases with F4 (4.4) as shown in table (8).The highest correlation was observed for Fibro Q (rs= 0.435), Lok's model (rs= 0.426), FIB-4 (rs= 0.426), API (0.323) and Pohl score (0.112) as shown in (Table 9).AAR, FibroQ, FIB-4, API, and Lok's model results increased significantly as the fibrosis advanced as shown in (table 10).For the prediction of mild fibrosis (F1 and F2); using a cutoff value of the Fibro Q score of >1.4 to predict the presence of significant fibrosis resulted in a sensitivity of 86%, specificity of 79.6%, PPV of 75.4%, and NPV of 90.6%.With AAR, the cut-off levels to predict the presence (AAR >2.4) of significant fibrosis had a sensitivity of 77.4% specificity of 63.6%, PPV of 72.6%, and NPV of 89.6%.Using APRI, the cutoff values to predict the presence (APRI >1.5) of significant fibrosis had a sensitivity of 77.6%, specificity of 81.6%, PPV of 72.6%, and NPV of 84.6% (Table 11).For the prediction of extensive fibrosis (F3 and F4), at a cutoff of Fibro Q >2.6 the sensitivity was 84.9%, specificity was79.6%,PPV was 68.7% and NPV was 78.3% and at a cutoff of FIB-4 >2.4, the sensitivity was 89.4%, specificity was 57.4%, PPV was 71.6% and NPV was 80.4% (Table 12).which has included 237(135 male and 102 female) patients showed that Pohl score and CDS had high specificity but low sensitivity, and their AUCs were not statistically different from 0.5.In addition, FibroQ, FIB-4, and Lok's model showed the best performance characteristics.The AUCs for predicting significant fibrosis were 0.789, 0.785 and 0.768, respectively.The AUCs for predicting extensive fibrosis were 0.728, 0.725 and 0.721, respectively [15,16].In the current study, the cut off value for FibroQ that could predict mild liver fibrosis was >1.4 with a sensitivity of 86% , specificity 79.6%, PPV 75.4% and NPV 90.6% ,while its cut off value that could predict extensive liver fibrosis was >2.3 with a sensitivity 86.9%, specificity 76.6%, PPV 68.7% and NPV 76.3%.These results came in agreement with Hsieh et al. [17] who showed that FibroQ has better accuracy than AAR and APRI.Using a cutoff value of the FibroQ score of > 1.6, the presence of significant fibrosis could correctly be identified with a high accuracy (93% PPV) in 92 (65%) of the 140 patients.Also Hsieh et al. [17] showed that among patients with a FibroQ score of 0.6 or less, five of nine (55.6%) did not have significant fibrosis.Among the 116 patients who had significant fibrosis, only four patients had FibroQ scores of 0.6 or less.Among patients with FibroQ scores of >1.6, 92 of 99 (92.9%) had significant fibrosis and only seven patients without significant fibrosis were classified incorrectly.Together, using the FibroQ below the lower cutoff value (0.6) and above the higher cutoff value (1.6), 108 of the 140 patients (77.1%) were identified correctly as with or without significant fibrosis.In this regard, these results were similar to that of APRI as described by Wai et al. [17].

CONCLUSION
The current study demonstrated that FibroQ, FIB-4, and Lok's model are simple methods that correlated well with the stages of fibrosis in patients with chronic hepatitis C. FibroQ showed a trend to be superior to the other modalities evaluated.Further prospective studies involving larger numbers of patients are needed to validate the usefulness of FibroQ in clinical practice.Funding: None.

Table ( 1 ) :
Comparison between the studied groups as regard age and sex

Table ( 5
): Comparison between the studied groups as regard ANA titer , Schistosomal Ab , TSH, Alpha feto-protein and random blood sugar

Table ( 6
): Comparison between the studied groups as regard AAR, APRI, API, CDS, FIB-4 index, FibroQ index and Pohl score These findings supported the results of Pohl et al. [14], Lackner et al. [41] and Fouad et al. [39] who confirmed the diagnostic accuracy of the Pohl score in significant fibrosis and cirrhosis.The results of previous study by Hsieh et al. [45]